The NONMEM Project at the University of California, San Francisco, which produced the UCSF NONMEM software, is concerned with the development of data analysis techniques and exportable software for fitting nonlinear mixed effects (statistical regression-type) models. These techniques are particularly useful when the data are population pharmacokinetic/pharmacodynamic data, and when there are only a few PK/PD measurements from some individuals sampled from the population, or when the regression design varies considerably between individuals. However, increasingly, the techniques are also being used advantageously with better-designed experimental type data.
As the software evolves, it reflects tested methodological and programming improvements. The UCSF NONMEM program first appeared in 1979; the current version of NONMEM is Version V of a later series. UCSF NONMEM Version V is licensed and distributed by GloboMax LLC. The software consists of three parts: The NONMEM program itself is a very general (noninteractive) regres- sion program which can be used to fit many different types of data. It can be used to simulate data, as well as fit data. PREDPP is a powerful pack- age of subroutines that can be used by NONMEM to compute predictions for population pharmacokinetic data. Use of PREDPP obviates the need for the user to code kinetic-type equations, and it also allows complicated patient-type data to be easily used. However, the user can also directly, and very generally, code prediction-type equations, and thus a great variety of different types of models can be used. NM-TRAN is a (nonin- teractive) preprocessor, allowing control and other needed inputs to NONMEM/PREDPP to be specified in a user-friendly manner, with quick and comprehensive detection of a variety of errors that the user may have made in so doing.
The three components are written and distributed in ANSI FORTRAN 77 code
and, therefore, can be used with any hardware and operating system incor-
porating a FORTRAN 77 compiler adhering to the ANSI standard. Since some
NONMEM runs can take considerable CPU time, perhaps many hours, depending
on the speed of the computer and the size of the problem, it is advisable
to use a fast machine. In addition to fast time-shared computers, 32-bit
PC's are commonly used, as are RISC machines of different sorts.
Certain system requirements should be noted.
1. At least 4 megabytes of memory, and preferably 12 megabytes, should be available for exclusive use of the NONMEM and NM-TRAN programs.
2. The FORTRAN compiler should allow:
hollerith constants and hollerith format specifications
the assignment of hollerith constants to integer variables in DATA statements
variables of different types to share the same storage area via an EQUIVALENCE statement
the default length of integer variables to be 4 bytes
the INCLUDE statement
Support for the user consists primarily in a series of documents:
NONMEM Users Guide I -- Users Basic Guide
NONMEM Users Guide II -- Users Supplemental Guide
NONMEM Users Guide III -- NONMEM Installation Guide
NONMEM Users Guide IV -- NM-TRAN Guide
NONMEM Users Guide V -- Introductory Guide
NONMEM Users Guide VI -- PREDPP Guide
NONMEM Users Guide VII -- Conditional Estimation Methods
NONMEM Users Guide VIII -- Help Guide
NONMEM V Supplemental Guide
Part I describes the basic use of the NONMEM program.
Part II describes more advanced use of the program.
Part III describes how to install NONMEM, PREDPP, and NM-TRAN.
Part IV describes the use of NM-TRAN.
Part V serves as an introduction to the complete NONMEM system.
Part VI describes the use of the PREDPP package.
Part VII describes the estimation methods used by the program.
Part VIII describes NONMEM system usage in the form of a Help document.
The Help Guide is accompanied by a diskette containing the same contents as the printed document, and also by another diskette containing software tools to be used with DOS systems for the on-line display of the Help Guide. The files on these diskettes may be stored on each of the same machines on which UCSF NONMEM is installed. The NONMEM V Supplemental Guide describes differences between NONMEM Ver- sions IV and V.
Consultation and courses, including hands-on beginning level workshops, are offered by GloboMax LLC. For further information, contact GloboMax LLC (see below). A phone and an electronic technical support line, as well as a listserve for NONMEM users (the NONMEM Users Network), are also provided by GloboMax LLC. Help with using the program is also available by means of a 3-day Basic Level Short Course and a 2-day Intermediate Level Workshop organized by the University of California, San Francisco, NONMEM Project Group. In addition, there are four geographically-based groups of NONMEM users, which meet annually.
The software and documentation comprise the Licensed Products. With a given license, NONMEM may be run at any given time on a specified number of separate computers at a common site, and on no more than this number of computers, even though all the computers at the site might be networked. The specified number is to be filled in on the UCSF NONMEM order form when an order is placed, and the order form becomes an attachment to the license. The term of the license is one (1) year, and the license is renewable each year thereafter. At each renewal time, the licensee at its option (as well as GloboMax LLC at its option) may choose not to renew the license. Each year an annual license fee is paid. The amount of the first year's fee, and that of a fee for a subsequent year, depends on the number of separate computers being currently used to run UCSF NONMEM. Each year at the time the license is renewed the fee is subject to change, because either the number of computers specified by the licensee at the renewal time changes from that specified at the previous time and/or, as may happen infrequently, the fee structure changes.
The UCSF NONMEM system is distributed on DOS formatted diskettes. Upon request, it can be provided on Unix-tar formatted diskettes. The media, along with one set of the documentation listed above, will be mailed when the license is issued. As long as a license is active, all updates and additions to the program and documentation will also be mailed, without additional charge for these items. Additional copies of any of the docu- ments may be purchased.
For ordering information or other information from GloboMax concerning NONMEM, contact:
GloboMax LLC
NONMEM Project Team
7250 Parkway Dr.
Suite 430
Hanover, MD 21076
USA
Last updated: October 17, 2001